Researchers find clues to autism in our genes and our gut

Researchers are now investigating the link between brain disorders, such as autism, and the health of our guts.Photo by
AFP

Autism spectrum disorder affects roughly four to five times as many males as females, and scientists are starting to understand why. It turns out that, from a genetic viewpoint, men may indeed be the weaker sex.

Their key finding was that females with these diagnoses had significantly more genetic abnormalities than similar males. This suggests that the female brain is more robust in some ways than the male brain, at least in terms of resisting these symptoms. Their work also tends to counteract the “social bias” hypothesis that boys are more likely than girls to be diagnosed with ASD because doctors are more likely to look for it in males.

Remembering high school genetics, one might think that the added robustness comes from the fact that females have two copies of the X chromosome, while males only have one. This is certainly true for a mental disability called Fragile X syndrome, in which the body is unable to make a key protein. Fragile X syndrome is more prevalent in males because the females have a “back-up” X chromosome. If that one is normal, they can make the required protein.

However, we now know that genes that relate to mental development show up across the genome. In fact, the Swiss researchers created a list of 1,560 candidate genes that may play a role in neurological disorders (NDs), though they acknowledge the list “included genes that might have been falsely associated in the literature with a particular ND.” While many of these are still something of a mystery, that tabulation demonstrates the impressive growth in our understanding of the genetic basis of neurological disease.

There are also epigenetic factors at play here. Epigenetics refers to changes in the genome that do not alter the underlying gene sequence, but can still have profound effects on how genes work. The actual changes usually involve chemical alterations to DNA (such as the addition of a methyl group). These can alter how a gene interacts with the machinery in the nucleus of the cell, effectively turning genes on and off. Environmental and other factors can play a role in causing epigenetic changes.

The implications of findings like this are that we may see the day when personalized therapies can be crafted to help combat particular neurological disorders in specific patients. In an article with colleagues, Akbarian suggests this may well happen: “Identification of the precise combinations of these aberrantly regulated gene sets in a particular disease case, including a potential association with the severity of specific disease symptoms, can bear great promise toward better understanding of the underlying neurobiology and, perhaps more importantly, could set the foundation for novel therapies specifically tailored toward individual patients.”

Another panel at the AAAS meeting focused on how something we do every day, eating, affects our brains. Researcher Elaine Y. Hsiao of the California Institute of Technology tackled “Gut-Brain-Immune Connections in Autism and Schizophrenia.” Her research provides some intriguing insights into how neurological disorders are caused, and may be treated.

In a paper published recently in Cell, Hsiao and other researchers describe how they caused autism-like symptoms in mice by injecting them with a virus-like molecule. Then, with the use of probiotics containing Bacteroides Fragilis, they were able to repair the barrier function of the gut, and also reduce the behavioural symptoms.

Of course, this is still in a mouse model, but these researchers make a fairly heady claim: “We propose the transformative concept that autism, and likely other behavioural conditions, are potentially diseases involving the gut that ultimately impact the immune, metabolic, and nervous systems, and that microbiome-mediated therapies may be a safe and effective treatment for these neurodevelopmental disorders.”

While it’s still early days for all of this work, this research opens up intriguing possibilities for the study and treatment of neurological disorders, and the future of personalized medicine. It also reminds us that, in some subtle ways, we are what eat.

Dr. Tom Keenan is an award winning journalist, public speaker, professor in the Faculty of Environmental Design at the University of Calgary, and author of the new book, Technocreep,www.orbooks.com/catalog/technocreep/

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